The MIC range of butenafine against dermatophytes is 0.03-0.25 μg/ml, indicating significant activity against them. Malassezia furfur is not affected by it, and it exhibits negligible activity against Candida albicans [1]. Promastigote forms of L were eliminated by butenafine (25, 50, or 100 μM). L. amazonensis and L. braziliensis in a dose-dependent fashion, exhibiting EC50 values in BALB peritoneal macrophages of 34.10 ± 3.76 μM, respectively. and mice at 81.25±10.24 μM/c. With a CC50 of 97.88 μM, butenafine exhibits mild cytotoxicity on peritoneal macrophages in BALB/c mice [1].

There is no effect of mouse butenafine (subcutaneous injection; 1-100 mg/kg) on the autonomic or central nervous systems. The somatic nervous system of guinea pigs after topical treatment of 0.3–3.0% butenafine solution is unaffected [1]. Butenafine (1% topical; 4–10 days; days 3 and 4 postinfection) was successful in vivo against dermatophytosis, Trichophyton mentagrophytes after 10 days Complete cure in a preliminary treatment study conducted in guinea pigs [1]. There is no difference in the efficacy between treating dermatophytosis, Trichophyton mentagrophytes in vivo, once daily or twice daily. Butenafine (0.125, 0.25, 0.5, and 1.0% applied topically; once daily or twice daily; day 4 postinfection) demonstrated 100% cure after application at 0.5% or 1%, and 1% per dose.

Absorption, Distribution and Excretion
The total amount absorbed through the skin into the systemic circulation has not been quantified. Metabolism/Metabolites The main metabolite in urine is formed via hydroxylation of the terminal tert-butyl side chain. Biological Half-Life Following topical application, a biphasic decrease in plasma butenafine concentration was observed, with an estimated initial half-life of 35 hours and a terminal half-life exceeding 150 hours.

Effects During Pregnancy and Lactation
◉ Overview of use during lactation No studies have been conducted on the use of butenafine during lactation. Due to poor absorption after topical application, it is unlikely to enter the infant's bloodstream and will not have any adverse effects on breastfed infants. Ensure that the infant's skin does not come into direct contact with the treated area. Water-soluble creams or gels should only be applied to the breast, as ointments may expose the infant to high concentrations of mineral oil through licking. [1] ◉ Effects on breastfed infants No relevant published information was found as of the revision date. ◉ Effects on lactation and breast milk No relevant published information was found as of the revision date.

[1]. Katrina Kokjohn, et al. Evaluation of in vitro activity of ciclopirox olamine, butenafine HCl and econazole nitrate against dermatophytes, yeasts and bacteria.Int J Dermatol. 2003 Sep;42 Suppl 1:11-7.
[2]. Adriana Bezerra-Souza, et al. The antifungal compound butenafine eliminates promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis. 2016 Dec;65(6 Pt A):702-707.
[3]. Topical Antifungal Agent. Butenafine

Butenafine is a trimethylamine in which hydrogen atoms attached to different methyl groups are replaced by 1-naphthyl and 4-tert-butylphenyl groups. It is an inhibitor of squalene epoxidase, an enzyme responsible for the synthesis of sterols required for fungal cell membranes. Butenafine hydrochloride is used to treat fungal skin infections. It is an EC 1.14.13.132 (squalene monooxygenase) inhibitor and antifungal drug. It is a tertiary amine belonging to the naphthalene class of compounds. Butenafine hydrochloride is a synthetic benzylamine antifungal agent. The mechanism of action of butenafine is believed to be related to the inhibition of sterol synthesis. Specifically, butenafine's mechanism of action is the inhibition of squalene epoxidase activity, an enzyme crucial for the formation of essential sterols for fungal cell membranes. Butenafine is a benzylamine antifungal drug. See also: Butenafine hydrochloride (salt form).

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Indications
For the topical treatment of the following skin infections caused by Malassezia furfur: tinea versicolor (Malassezia furfur infection), tinea pedis (athlete's foot), tinea corporis (ringworm), and tinea cruris (jock itch). These fungi include Epidermophyton floccosum, Trichophyton mentagrophytes, Trichophyton rubrum, and Trichophyton tonsurans.
FDA Label

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Mechanism of Action
While its mechanism of action is not fully elucidated, studies have shown that butenafine, similar to allylamines, interferes with…butenafine inhibits the biosynthesis of sterols, particularly ergosterol, by inhibiting squalene monooxygenase (an enzyme responsible for converting squalene to 2,3-oxosqualene). Since ergosterol is an important component of the fungal cell membrane, inhibition of its synthesis leads to increased cell membrane permeability, resulting in leakage of cell contents. Blockage of squalene monooxygenase also leads to the accumulation of squalene. At higher concentrations, squalene is believed to have a direct killing effect on fungal cells.

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Pharmacodynamics
Butenafine is a synthetic antifungal drug whose structure and pharmacological properties are related to allylamine antifungal drugs. Its exact mechanism of action is not yet clear, but studies have shown that butenafine's antifungal activity is achieved by altering the cell membrane, leading to increased membrane permeability and thus inhibiting fungal growth. Butenafine is primarily effective against dermatophytes, exhibiting superior fungicidal activity against these fungi compared to terbinafine, naftifine, tolnaftate, clotrimazole, and bifonazole. It is also effective against Candida albicans, with superior activity compared to terbinafine and naftifine. Furthermore, butenafine has lower minimum inhibitory concentrations (MICs) against Cryptococcus neoformans and Aspergillus spp.

C23H27N

317.46718

317.214

101828-21-1

Butenafine Hydrochloride;101827-46-7

2484

Typically exists as solid at room temperature

1.0±0.1 g/cm3

426.1±14.0 °C at 760 mmHg

187.7±17.0 °C

0.0±1.0 mmHg at 25°C

1.598

6.77

0

1

5

24

374

0

ABJKWBDEJIDSJZ-UHFFFAOYSA-N

InChI=1S/C23H27N/c1-23(2,3)21-14-12-18(13-15-21)16-24(4)17-20-10-7-9-19-8-5-6-11-22(19)20/h5-15H,16-17H2,1-4H3

1-(4-tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)methanamine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)